17-9918089-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_201433.2(GAS7):​c.1229G>A​(p.Arg410Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000564 in 1,612,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

GAS7
NM_201433.2 missense

Scores

1
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87
Variant links:
Genes affected
GAS7 (HGNC:4169): (growth arrest specific 7) Growth arrest-specific 7 is expressed primarily in terminally differentiated brain cells and predominantly in mature cerebellar Purkinje neurons. GAS7 plays a putative role in neuronal development. Several transcript variants encoding proteins which vary in the N-terminus have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.024041384).
BS2
High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GAS7NM_201433.2 linkc.1229G>A p.Arg410Gln missense_variant Exon 13 of 14 ENST00000432992.7 NP_958839.1 O60861-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GAS7ENST00000432992.7 linkc.1229G>A p.Arg410Gln missense_variant Exon 13 of 14 1 NM_201433.2 ENSP00000407552.2 O60861-3

Frequencies

GnomAD3 genomes
AF:
0.000230
AC:
35
AN:
152262
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.0351
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250694
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135508
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000383
AC:
56
AN:
1460720
Hom.:
0
Cov.:
30
AF XY:
0.0000344
AC XY:
25
AN XY:
726738
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000376
Gnomad4 NFE exome
AF:
0.0000468
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000230
AC:
35
AN:
152262
Hom.:
0
Cov.:
33
AF XY:
0.000229
AC XY:
17
AN XY:
74392
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000572
Hom.:
0
Bravo
AF:
0.000344
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1229G>A (p.R410Q) alteration is located in exon 13 (coding exon 13) of the GAS7 gene. This alteration results from a G to A substitution at nucleotide position 1229, causing the arginine (R) at amino acid position 410 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.080
T
BayesDel_noAF
Benign
-0.26
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.031
.;.;T;.;.;.;T;.
Eigen
Uncertain
0.24
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Pathogenic
0.98
.;.;D;D;D;.;D;D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.024
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.81
.;.;L;.;.;.;.;.
PrimateAI
Uncertain
0.67
T
REVEL
Benign
0.10
Sift4G
Benign
0.091
T;T;T;T;T;T;D;T
Polyphen
0.97, 0.81
.;.;D;.;P;.;.;.
Vest4
0.72
MutPred
0.24
.;.;Loss of helix (P = 0.2022);.;.;.;.;.;
MVP
0.56
MPC
2.0
ClinPred
0.83
D
GERP RS
5.1
Varity_R
0.15
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs749184881; hg19: chr17-9821406; API